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Resveratrol-Loaded Phytomedicines for Management of Cancer
Published in Mahfoozur Rahman, Sarwar Beg, Mazin A. Zamzami, Hani Choudhry, Aftab Ahmad, Khalid S. Alharbi, Biomarkers as Targeted Herbal Drug Discovery, 2022
Shakir Saleem, Ruqaiyah Khan, Sandeep Arora
Progression of tumor implies the growth in size and increase in a number of cells in the tumor. This progression implicates various processes such as that lead to tumor metastasis. It has been seen that several genes are mutated or deleted physiologically that sustain the development of aggressive tumors. The invasion of healthy cells and metastasis of cancerous cells include the destruction of the extracellular matrix (ECM) and the basement membrane, by proteolytic enzymes, such as matrix metalloproteinases (MMPs). Out of all these enzymes, MMP-2 and MMP-9 are highly expressed within different types of malignant tumors modifying the cellular invasion and its metastatic properties (Nelson et al., 2000). Tissue inhibitor metalloproteinase proteins (TIMPs), on the other hand, are a protein group comprising TIMP-1, -2, -3, and -4 acting as natural MMP inhibitors (Jinga et al., 2006). Invasive tumors require new blood vessels which are fulfilled via angiogenesis. During the process of angiogenesis, endo-thelial cells can be activated by several growth factors, like fibroblast growth factor (FGF) and VEGF. Obstructing the development of newly formed blood vessels causes the supply of nutrients and oxygen to be reduced and, as a result, the size of the tumor and metastasis may also be reduced (see Table 12.3).
Tocotrienol Vitamin E and Neurodegenerative Disorders
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Neuroprotection alone is not an effective strategy to mitigate damage from ischemic stroke [39]. Arteriogenesis in response to a pathology is marked by the early expression of tissue inhibitor of metalloproteinase 1 (TIMP1) in growing collateral vessels. TIMP-1 is a glycoprotein responsible for the inhibition of matrix metalloproteinase 2 (MMP2). TIMP1 binds to MMP2 in a 1:1 stoichiometric ratio to inactivate it and provide control of MMP2 activity. TIMP1 upregulation correlates with increased angiogenic activity by locally inhibiting MMP2 [45]. Tocotrienol supplementation in canines improved blood flow in collateral vessels and improved poststroke arteriogenesis by upregulating TIMP1 expression and inhibiting MMP2 activity (Figure 14.2) [36].
Hyaluronidase and Gelatinase (MMP-2, MMP-9) Inhibitor Plants
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Assessment of Medicinal Plants for Human Health, 2020
C. Donmez, G. D. Durbilmez, H. El-Seedi, U. Koca-Caliskan
Although both have substantial effects, level of HA and gelatin in the skin decreases due to aging, improper diet, stress, and various external factors, such as sunlight, wind, irritation, injury, and cigarette smoke. The degradation of HA and gelatin is undesirable in terms of maintaining vitality and flexibility of the skin. “Replacement therapy”, “increasing the synthesis of the related enzymes”, and “inhibiting their disintegration” on the skin are some of the solutions to keep the level of the enzymes at desirable levels. “Hyaluronidase” is an enzyme that catalyzes the degradation of HA. “Gelatinase A and B” (also known as “matrix metalloproteinase (MMP)-2 and MMP-9”) are members of the matrix metalloproteinase enzyme family to catalyze the degradation of gelatin.
Treatment of malignant pleural effusion in non-small cell lung cancer with VEGF-directed therapy
Published in Annals of Medicine, 2022
Zhangqiang Xiang, Xiangyu Deng, Wenfeng He, Qian Yang, Laichao Ni, Marzieh Dehghan Shasaltaneh, Mazaher Maghsoudloo, Gang Yang, Jingbo Wu, Saber Imani, Qinglian Wen
The combination of BEV, APA and CDDP inhibited neo-angiogenesis in the LLC xenografts by blocking the MAPK/ERK and Ras/Raf/MEK/ERK pathways, and had a more pronounced effect on HIF-1α and MMP-2 than either drug alone. HIF-1 is the key activator of hypoxia-induced angiogenesis and is regulated by the tumour suppressor gene von Hippel Lindau (VHL). Under normoxic conditions, HIF-1α is rapidly degraded by the ubiquitin-proteasome pathway under the control of VHL. However, hypoxia or VHL deletions/mutations results in the heterodimerization of HIF-1α and HIF-1β, which then translocates to the nucleus and activates VEGF transcription [73]. MMP-2 is an oncogenic protein that degrades extracellular matrix proteins and triggers mediates matrix remodelling and vascularization [74]. It lies downstream of the VEGF signalling cascade and plays an important role in the invasion and metastasis of tumour cells. Studies show that binding of VEGF with VEGFR-2 receptor induces dimerization of the latter, which promotes tumour angiogenesis by activating the C-RAF-MEK-MAPK pathway [75,76]. VEGF/VEGFR-2 interaction also increases microvascular permeability, and the proliferation, invasion, migration and survival of endothelial cells [77,78]. As shown in Figure 9, CDDP, APA and BEV simultaneously target different intermediates in the VEGF-induced MAPK/ERK signalling pathway and NRF2-dependent antioxidant response pathways, which enhances the anti-tumour effect.
High-protein diet associated with resistance training reduces cardiac TNF-α levels and up-regulates MMP-2 activity in rats
Published in Archives of Physiology and Biochemistry, 2022
Murilo Esteves Nogueira, Ivo Vieira Sousa Neto, Daisy Motta-Santos, Ana Paula de Castro Cantuária, Stella Maris de Freitas Lima, Taia Maria Berto Rezende, Hugo Alexandre de Paula Santana, Bernardo Assis Petriz, Rita de Cássia Marqueti, Jeeser Alves Almeida
Previously it was believed that the benefits of HPD on obesity could extend to the cardiovascular system (Gardner et al.2007). Afterward, prospective studies reported an increase in cardiovascular risk associated with HPD (Bernstein et al.2010; Lagiou et al.2012; Virtanen et al.2019). Additionally, Foo et al. (2009) and, more recently, Zhang et al. (2020) confirmed the atherogenic effect of HPD in an animal model. However, the role of high-protein consumption in cardiac molecular outcomes is still unknown. To date, data upon the effects of HPD and resistance training (RT) on cardiac biomarkers are contrasting (Melo et al.2018; Mittendorfer et al.2020). On the other hand, RT reduces pro-inflammatory cytokines and modulates the activity of metalloproteinase (MMPs) in the left ventricle of rats (Alves et al.2014; Barboza et al.2016). Thus, MMP-2 stands out as an essential enzyme in the regulation of the extracellular matrix and play an essential role in cardiac tissue (Guzzoni et al.2017; Leite et al.2013). Besides, RT induces angiogenesis through the convergence of numerous signalling mechanisms, which includes the activity of MMP-2, nitric oxide and the vascular endothelial growth factor (VEGF), which signal for improved oxygenation cardiac, microvascular and metabolic integrity (Ghorbanzadeh et al.2017; Milkiewicz et al.2005).
Investigation of anticancer activities of STA-9090 (ganetespib) as a second generation HSP90 inhibitor in Saos-2 osteosarcoma cells
Published in Journal of Chemotherapy, 2021
Bone remodelling and bone morphogenetic proteins (BMPs) related signalling pathways are essential to understand pathogenesis of osteosarcoma.49,50 BMPs are identified as the main source of ectopic bone formation but their molecular mechanisms in osteosarcoma is not fully understood yet. Pre-clinical and clinical studies reported that BMP2 and BMP7 exhibit inhibitory effect in proliferation and metastases processes of osteosarcoma cells. BMP7 inhibits telomerase activity in cancer cells.51 In addition, BMP2 increases the tendency for osteosarcoma to undergo apoptosis.52 PCR array results indicated that expression levels of the BMP2 and BMP7 genes were increased in STA-9090 treated Saos-2 cells. Matrix metalloproteinase 2 (MMP2) is an important member of the zinc-dependent endopeptidases which is confirmed to be related with the invasion and metastasis of many cancer types. Therefore, MMP2 has been significant target to develop new generation drugs in cancer treatment.53–55 In this study, MMP2 gene expression was found to be decreased in osteosarcoma cells treated with STA-9090. SPARC is identified as bone remodelling related gene which is closely related with pathogenesis of osteosarcoma. SPARC gene is over-expressed in osteosarcoma cells and lung metastasis tends to be induction with SPARC expression.56,57 In this study, SPARC gene showed significant loss of expression in STA-9090 treated osteosarcoma cells.